S100A8型
S100A9型
转录组
人口
整合素αM
免疫荧光
川地68
纤维化
巨噬细胞
生物
生物标志物
病理
分子生物学
免疫系统
基因
基因表达
抗体
免疫学
炎症
免疫组织化学
体外
医学
遗传学
环境卫生
作者
Rafael Ospino,Alexandra J. Berges,Laura M Mafla,Samuel Collins,Yee Chan‐Li,Ioan Lina,Alexander Gelbard,Alexander T. Hillel,Kevin Motz
出处
期刊:Laryngoscope
[Wiley]
日期:2022-12-16
卷期号:133 (9): 2308-2316
被引量:2
摘要
Idiopathic subglottic stenosis (iSGS) is characterized by progressive fibrosis and subglottic luminal narrowing. Currently, immune characterization has focused on T-cells; however, macrophages remain largely unexplored. The goals of this study are to characterize the transcriptome of iSGS macrophages and the fibrogenic nature of identifed biomarkers.Bioinformatics and in vitro.Human tracheal biopsies from iSGS scar (n = 4), and matched non-scar (n = 4) regions were analyzed using single-cell RNA-seq (scRNA-seq). Immunofluorescence (IF) was performed on rapidly processed autopsies (RPA) and iSGS tracheal resections (n = 4) to co-localize S100A8/9 and CD11b. Collagen gene/protein expression was assessed in iSGS fibroblasts (n = 4) treated with protein S100A8/9 (1000 ng/ml). Macrophages were subclustered to identify distinct subpopulations.scRNA-seq analysis revealed S100A8/S100A9 (fold change (FC) = 4.1/1.88, p < 0.001) as top differentially expressed genes in iSGS macrophages. IF exhibited increased CD11b+/S100A8/9+ cells in tracheal samples of iSGS versus RPA (26.75% ± 7.08 vs. 0.594% ± 0.974, n = 4, p = 0.029). iSGS fibroblasts treated with S100A8/9 demonstrated increased gene expression of COL1A1 (FC = 2.30 ± 0.45, p = 0.03, n = 4) and COL3A1 (FC = 2.44 ± 0.40, p = 0.03, n = 4). COL1A1 protein assays revealed an increase in the experimental group, albeit not significant, (p = 0.12, n = 4). Finally, macrophage sub clustering revealed one subpopulation as a predominant source of S100A8/S100A9 expression (FC = 7.94/5.47, p < 0.001).S100A8/9 is a key biomarker in iSGS macrophages. Although S100A8/9 demonstrates profibrotic nature in vitro, the role of S100A8/9+ macrophages in vivo warrants further investigation.NA Laryngoscope, 133:2308-2316, 2023.
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